Chapter 5 – Experimental fear 149 Introduction Negative expectations regarding an inert treatment stimulus have been shown to increase perceived pain intensity, as compared to perceived pain intensity in an untreated, control condition 1–5. This phenomenon has been termed nocebo hyperalgesia 1,6. In experimental studies negative suggestions and classical conditioning play key roles in the acquisition of nocebo hyperalgesia 7–10. Negative suggestions regarding the effects of a (sham) treatment on pain and the pairing of this treatment with increased pain administrations can produce negative expectations about this treatment 8,11. As a result of this learned negative expectation, an inert treatment can evoke increased pain sensitivity 9. Expectations installed by classical conditioning and aversive (threat/fear) conditioning are closely intertwined procedurally, but nocebo research has not systematically focused on the role of fear. A focus on fear is important as cognitive-affective neural processing has been implicated in nocebo hyperalgesia 4,12–14, with numerous studies showing a specific role of the amygdala, a primary fear processing region, in nocebo, but not placebo effects 4,15,16. Studies have used varying pain levels to induce nocebo hyperalgesia, ranging from as low as 5 to as high as 10 on 0 (no pain) to 10 (highest pain imaginable) rating scales 5,12,17–19. These pain intensities may differentially induce fear and as such influence nocebo responses. Furthermore, the threatening nature of suggestions also varies between experimental nocebo models. For example, Geuter and Büchel 18 used the negative suggestion that a capsaicin cream would momentarily increase perceived pain, while Benedetti and colleagues 17 suggested that participants may experience severe headaches during a mountaineering trip lasting several days. Whether such differences in perceived pain intensities, threatening
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